Unit of Synthesis and Biomedical Applications of Peptides, Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain.
Arthritis Unit, Hospital Clinic, Barcelona, Spain.
PLoS One. 2019 May 2;14(5):e0215927. doi: 10.1371/journal.pone.0215927. eCollection 2019.
Anti-citrullinated peptide/protein antibodies (ACPAs) are the most specific serological biomarkers for rheumatoid arthritis (RA). They have both diagnostic and prognostic value, and are related to more aggressive joint disease in RA. However, a single biomarker cannot differentiate RA subtypes. So, simultaneous analysis of target citrullinated peptides, using a multiplex array based on chimeric peptides composed of several domains of human proteins, could be useful. In this work, eight chimeric peptides and the corresponding native arginine-containing control peptides were obtained by solid-phase peptide synthesis. The study included RA and psoriatic arthritis (PsA) patients attending the Rheumatology Unit of the Hospital Clinic in Barcelona, as well as healthy blood donors (BD) at the same hospital. Our main aim was to explore the diagnostic value of the novel multiplex array compared to a commercial ELISA-based ACPA assay in a serum-saving way. Using the combination of the eight chimeric peptide antigens in the multiplex array, 61.4% of the RA cohort were positive for 3 or more peptides; while, the healthy BD and PsA cohorts did not show any reactivity with the tested peptides. These results indicate that we have developed a highly specific multiplex assay based of chimeric citrullinated peptides derived from filaggrin, fibrin, vimentin and human enolase proteins for the detection of ACPAs in a serum-saving way.
抗瓜氨酸化肽/蛋白抗体（ACPAs）是类风湿关节炎（RA）最特异的血清学生物标志物。它们具有诊断和预后价值，与 RA 更具侵袭性的关节疾病有关。然而，单一的生物标志物无法区分 RA 亚型。因此，同时分析靶向瓜氨酸化肽，使用基于由几种人蛋白域组成的嵌合肽的多重阵列可能是有用的。在这项工作中，通过固相肽合成获得了 8 个嵌合肽和相应的天然含精氨酸对照肽。该研究包括在巴塞罗那 Clinic 医院风湿病科就诊的 RA 和银屑病关节炎（PsA）患者，以及来自同一医院的健康献血者（BD）。我们的主要目的是探索新型多重阵列与基于商业 ELISA 的 ACPA 检测在节省血清的方式下的诊断价值。使用多重阵列中的 8 种嵌合肽抗原的组合，61.4%的 RA 队列对 3 种或更多肽呈阳性；而健康的 BD 和 PsA 队列则没有对测试肽表现出任何反应性。这些结果表明，我们已经开发了一种基于源自丝聚蛋白、纤维蛋白、波形蛋白和人烯醇化酶蛋白的嵌合瓜氨酸化肽的高度特异的多重分析，以节省血清的方式检测 ACPAs。
